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Parathyroid Hormone-Related Protein (PTHrP): A Key Regulator of Life/Death Decisions by Tumor Cells with Potential Clinical Applications
Cancers 2011, 3(1), 510-530; doi:10.3390/cancers3010510

Nerve Growth Factor in Cancer Cell Death and Survival

Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland
* Author to whom correspondence should be addressed.
Received: 7 December 2010 / Revised: 24 January 2011 / Accepted: 25 January 2011 / Published: 1 February 2011
(This article belongs to the Special Issue Cell Death and Cancer)
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One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.
Keywords: apoptosis; breast cancer; nerve growth factor (NGF); p75 neurotrophin receptor (p75NTR); prostate cancer; TrkA apoptosis; breast cancer; nerve growth factor (NGF); p75 neurotrophin receptor (p75NTR); prostate cancer; TrkA
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Molloy, N.H.; Read, D.E.; Gorman, A.M. Nerve Growth Factor in Cancer Cell Death and Survival. Cancers 2011, 3, 510-530.

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